Evaluation of Prednisolone with Clofutriben (SPI-62) or Placebo in Polymyalgia Rheumatica Patients: A Dose Adjustment Study

The primary objective of this clinical trial is to determine whether a **prednisolone** dose adjustment is necessary to maintain equivalent efficacy when administered in combination with **SPI-62** in subjects with polymyalgia rheumatica (PMR). This is clinically relevant as it aims to optimize treatment regimens for PMR, potentially improving patient outcomes by ensuring effective symptom management while minimizing adverse effects associated with inappropriate dosing.

Secondary objectives include:

• Observing whether SPI-62 mitigates prednisolone toxicity in subjects with PMR and estimating the appropriate dose for combination therapy.
• Characterizing the pharmacological activity of SPI-62 in subjects with PMR.
• Reporting the safety profile of SPI-62 in subjects with PMR treated with prednisolone.

The clinical trial involves participants diagnosed with **polymyalgia rheumatica (PMR)**, aiming to assess the necessity of prednisolone dose adjustment when administered with SPI-62. The study population includes both male and female subjects, with an age range that corresponds to categories 3 and 4, indicating a middle-aged to older adult demographic. Participants are required to have a stable daily oral prednisolone dose of 10 mg, which must have been consistent for at least one week prior to the baseline visit and is expected to remain stable throughout the treatment period. The trial includes a vulnerable population, although specific details regarding the total number of participants have not been provided by the sponsor. The selection criteria emphasize the absence of PMR relapse, as determined by symptoms and acute phase markers, ensuring that participants are in a stable phase of the condition. Lifestyle factors such as diet and physical activity are not specified, and the trial does not focus on any particular habits. The inclusion of both genders and the consideration of vulnerable populations highlight the trial's comprehensive approach to understanding the treatment's efficacy across a diverse group of individuals.

The clinical trial is designed to evaluate the efficacy of **prednisolone** in combination with SPI-62 or placebo in participants diagnosed with **polymyalgia rheumatica** (PMR). This is a Phase IV, randomized, double-blind, controlled trial. The primary objective is to determine if a dose adjustment of prednisolone is necessary when administered with SPI-62 to achieve equivalent efficacy. The trial is expected to conclude by May 31, 2025, with recruitment having commenced on August 26, 2022.

Participants will be involved in the study for a maximum treatment period of 28 days. The trial includes several key visits: an initial screening visit to confirm eligibility based on criteria such as a stable daily oral prednisolone dose of 10 mg, followed by a baseline visit where treatment begins. Follow-up visits will be scheduled to monitor the primary endpoints, including fibrinogen, erythrocyte sedimentation ratio, and C-reactive protein levels, as well as secondary endpoints like oral glucose tolerance test glucose area under the curve, osteocalcin, and urinary 11β-hydroxysteroid dehydrogenase type 1 ratio. The end-of-study visit will assess the overall outcomes and any adverse events.

Participant involvement is expected to last up to 28 days, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with the study protocol. The trial employs a double-blind design, with participants randomly assigned to receive either the active treatment or placebo, ensuring unbiased results. The study's methodology is structured to maintain scientific rigor and integrity, with all substances administered orally in tablet form. The trial's findings aim to provide insights into the optimal dosing strategy for prednisolone when used in conjunction with SPI-62 in the management of PMR.

The clinical trial involves the administration of **Prednisolone**, marketed as Prednisolon 5 mg JENAPHARM, which is provided in tablet form. The active substance, **prednisolone**, is a chemically derived corticosteroid. Participants will receive a maximum daily dose of 20 mg, with a total maximum dose of 560 mg over a treatment period of 28 days. The tablets are administered orally. To maintain the single-blind nature of the study, prednisolone is over-encapsulated. Participant compliance will be monitored through regular assessments and pill counts.

Another experimental medication used in the trial is **Clofutriben**, available under the product names SPI-62_DF1 and SPI-62_DF2, both in film-coated tablet form. The active substance, **clofutriben**, is also chemically synthesized. The maximum daily dose for clofutriben is 6.0 mg, with a total maximum dose of 84 mg over a 14-day treatment period. The administration route is oral. Compliance with the dosing schedule will be monitored through participant diaries and periodic checks.

The study also includes the use of placebo treatments to maintain the integrity of the trial design. A hard capsule is used as a placebo for prednisolone, and a film-coated tablet serves as a placebo for clofutriben (SPI-62). These placebos are administered orally, mirroring the administration routes of their respective active counterparts. The placebo treatments are designed to be indistinguishable from the active medications to ensure blinding is maintained throughout the study.

The efficacy of the clinical trial involving **polymyalgia rheumatica (PMR)** will be assessed using both primary and secondary endpoints. The primary endpoints include the measurement of fibrinogen, erythrocyte sedimentation ratio, and C-reactive protein levels. These biomarkers are critical in evaluating the inflammatory response and disease activity in participants. Secondary endpoints will focus on metabolic and bone health parameters, including the oral glucose tolerance test glucose area under the concentration-time curve, osteocalcin levels, and the urinary 11β-hydroxysteroid dehydrogenase type 1 ratio.

Data collection for these endpoints will be conducted at specified intervals throughout the trial. The trial aims to determine if a dose adjustment of prednisolone is necessary when administered with SPI-62 to achieve equivalent efficacy in subjects with PMR. The trial is designed as a Phase IV study, indicating its focus on post-marketing surveillance to further explore therapeutic effects and safety. The trial is not categorized as low intervention, reflecting its exploratory nature in assessing the combination treatment's efficacy and safety profile.